Lack of WRN results in extensive deletion at nonhomologous joining ends.

Abstract

Loss of WRN causes the genomic instability progeroid syndrome, Werner syndrome. WRN encodes a multifunctional nuclear protein with 3'-->5' exonuclease and 3'-->5' helicase activities. Linear plasmids with noncompatible ends introduced to Werner syndrome cells underwent extensive deletions at nonhomologous joining ends, particularly at the 3' protruding single-stranded end. This extensive deletion phenotype was complemented by wild-type WRN. These results suggest that WRN can out-compete other exonucleases that participate in double-strand break repair or stabilize the broken DNA end.